SO051PROSPECTIVE OPEN-LABEL EXPLORATIVE RANDOMISED SINGLE CENTRE COMPARATIVE STUDY TO DETERMINE THE EFFECTS OF VARIOUS INTRAVENOUS IRON PREPARATIONS ON HAEMOGLOBIN, HAEMETENICS, MARKERS OF KIDNEY FUNCTION, QUALITY OF LIFE AND SAFETY

Abstract

Abstract Background and Aims Iron deficiency in Chronic Kidney Disease (CKD) is common. It frequently necessitates the use of intravenous (IV) iron for correction. A number of second and third generation preparations are now in clinical use with potentially increased efficacy and improved safety profiles. Concerns remain regarding the potential impact of intravenous iron on oxidative stress, kidney function, inflammation and endothelial function, which in turn may represent non-traditional cardiovascular risk factors. The aim of this study is to verify whether three different IV iron preparations have similar safety, efficacy and effects on oxidative stress, inflammation, endothelial and renal function in a non-dialysis CKD population in the short term. Method This was a prospective open-label exploratory randomized, single-centre study comparing the efficacy and safety of three parenteral iron formulations (Iron Dextran (ID), Iron Sucrose (IS) and Iron Isomaltoside (IIM)). Patients with established CKD stages 3-5 and ferritin (SF) < 200microg/L and/or transferrin saturation (TS) <20% were recruited. They were randomized in a 1:1:1:1 ratio receiving a single infusion of ID 200mg IS 200mg, or IIM either at a low (200mg) or high dose (1000mg). Follow-up took place at 2 hours, 1 day, 1 week, 1 month and 3 months post-infusion. Response to iron was assessed using haemoglobin, TS and SF. Kidney function (Creatinine (Cr), eGFR) and proteinuria as a marker of injury (protein:creatinine, albumin:creatinine) were monitored. C-reactive protein (CRP) was used as an inflammatory indicator. Arterial response was monitored using Pulse wave velocity (PWVI). Quality of Life was assessed via the SF-36 questionnaire. Adverse events (AEs) were captured throughout the study, recorded for safety analysis and evaluation of relationship to treatment. Data is presented as means and standard error of the mean (SEM). Statistical analysis was carried out using ANOVA. A p value of <0.05 was statistically significant. Results: Forty patients were recruited and randomized ten to each group; 58% of the patients were male. The mean age was 58.8 years (±2.2). TS and SF rose in response to iron. Greater and more lasting ferritin repletion was seen in the group receiving 1000mg of IIM (pre-dose: 69.1 microg/L (±18.4); 3 months: 271.0 microg/L (±83.3)). All IV iron preparations led to a significant but transient rise in TS within the first 2 hours especially IIM 1000 group (17.8% to 98.7%; p-value <0.001) and IS (21.1% to 91.4%; p-value<0.01) to values >90%. These returned to baseline within 1 week. There was no statistical difference in haemoglobin concentration throughout both cumulatively and comparatively. CRP increased within one day but returned to normal values within one week – this was most pronounced with IS (pre-dose CRP: 8.1 (±3.3) 1-day CRP: 36.1 (±27.0); p=0.29). There was no short-term impact on renal function; mean Cr pre-dose: 234.6 umol/L (±16.6), to 216.6umol/L (±16.2) and mean eGFR pre-dose: 28.2 ml/min (±2.2) to 28.5 ml/min (±2.5). Proteinuria following infusion with IV iron was unchanged (pre-dose: 154.2 mg/mmol (±48.4); 2-hours post-dose: 127.5 mg/mmol (±45.2). Arterial stiffness (PWVI) did not increase following IV iron infusion irrespective of preparation or dosage. Quality of Life improved, which was more evident one month following infusion (pre-dose: 47.7 (±3.8); post-dose 54.4 (±4.3). There was one serious AE in the IIM high dose group with a death more than 2 weeks following infusion likely unrelated to infusion. Conclusion Both high and low dose intravenous irons are effective in replenishing the iron stores with significant increase in iron biomarkers. In the short-term there was no impact on kidney function, inflammation or vascular function. Intravenous iron, irrespective of impact on haemoglobin, translates to improvement in quality of life. Larger and more long-term studies are required to further assess safety.